The objectives of this proposal are to identify those host immune and non-immune functions that protect mice from the lethal effects of murine cytomegaloviruses (MCMV) infection. MCMV has been shown to interfere with the development of humoral immunity, interferon production and T cell function and is significantly more lethal for weanling than adult mice. The roles of tissue support of virus replication, humoral antibody, macrophages and cell-mediated immunity will be defined in experimental infections. We plan to compare these functions in mice with lethal and nonlethal infections. These mice will be functionally intact or compromised due to immaturity or experimental manipulation.